The light-from-above prior is intact in autistic children

Sensory information is inherently ambiguous. The brain disambiguates this information by anticipating or predicting the sensory environment based on prior knowledge. Pellicano and Burr (2012) proposed that this process may be atypical in autism and that internal assumptions, or “priors,” may be underweighted or less used than in typical individuals. A robust internal assumption used by adults is the “light-from-above” prior, a bias to interpret ambiguous shading patterns as if formed by a light source located above (and slightly to the left) of the scene. We investigated whether autistic children (n = 18) use this prior to the same degree as typical children of similar age and intellectual ability (n = 18). Children were asked to judge the shape (concave or convex) of a shaded hexagon stimulus presented in 24 rotations. We estimated the relation between the proportion of convex judgments and stimulus orientation for each child and calculated the light source location most consistent with those judgments. Children behaved similarly to adults in this task, preferring to assume that the light source was from above left, when other interpretations were compatible with the shading evidence. Autistic and typical children used prior assumptions to the same extent to make sense of shading patterns. Future research should examine whether this prior is as adaptable (i.e., modifiable with training) in autistic children as it is in typical adults

P863 KEYNOTE-022 parts 4 and 5: pembrolizumab plus trametinib for patients with solid tumors or BRAF wild-type melanoma

Background Pembrolizumab+dabrafenib+trametinib demonstrated promising antitumor activity and acceptable tolerability in BRAF-mutant melanoma in phase 1/2 KEYNOTE-022 parts 1 and 2 (NCT02130466). Pembrolizumab+dabrafenib+trametinib numerically prolonged PFS and DOR versus placebo+dabrafenib+trametinib but had a higher grade 3-5 TRAE rate in part 3. KEYNOTE-022 parts 4 and 5 evaluated pembrolizumab+trametinib. Methods In part 4 (open-label, 3+3 dose-finding) patients with advanced solid tumors (irrespective of BRAF status) or unresectable/metastatic BRAF wild-type melanoma received pembrolizumab 200 mg Q3W with trametinib as concurrent (2 or 4 weeks of trametinib run-in [1.5 or 2 mg QD], then pembrolizumab+trametinib [1.5 or 2 mg QD]) or intermittent dosing (2 weeks of trametinib run-in [1.5 or 2 mg QD], then pembrolizumab+trametinib [1.5 or 2 mg QD; 1 week off/2 weeks on]). Interim MTDs identified in part 4 were confirmed in part 5 using a modified toxicity probability interval design. The primary objectives were safety, tolerability, and ORR by investigator assessment per RECIST v1.1 of the maximum administered or tolerated dose (MAD/MTD) of pembrolizumab+trametinib. Safety was analyzed for all patients who received ≥1 dose of study drug; patients treated during the trametinib run-in who discontinued study before receiving pembrolizumab were included; patients who did not complete trametinib run-in or receive ≥66% of planned doses during the 6-week dose-limiting toxicity (DLT) evaluable period were not included for DLT evaluation. AEs were graded per NCI CTCAE v4. Results Of 42 enrolled patients, most were female (61.9%); median age was 55.0 years; 57.1% had received ≥2 prior lines of therapy. At database cutoff (June 26, 2019), median follow-up was 9.0 months (range, 1.4-25.6 months). Of 38 DLT-evaluable patients, 10 had DLTs (table 1). Dosing regimens were selected for confirmation in part 5 based on safety data. Any-grade TRAEs occurred in 39 (92.9%) patients; grade 3-4 TRAEs occurred in 19 (45.2%), none were grade 5. TRAEs led to discontinuation in 8 (19.0%) patients. Immune-mediated AEs occurred in 12 (28.6%) patients, most commonly severe skin reactions (n=6; 14.3%), pneumonitis (n=3; 7.1%), hypothyroidism (n=2; 4.8%). The MTD of concurrent pembrolizumab+trametinib was pembrolizumab 200 mg Q3W plus trametinib 1.5 mg with 2 weeks of trametinib run-in (ORR, 0/16; 0%) and the MTD of intermittent pembrolizumab+trametinib was pembrolizumab 200 mg Q3W plus trametinib 2 mg with 2 weeks of run-in (ORR, 4/15; 26.7%). Conclusions Both concurrent or intermittent pembrolizumab+trametinib dosing were feasible and the combination showed antitumor activity in patients with advanced solid tumors or advanced BRAF wild-type melanoma

The capabilities of people with intellectual and developmental disabilities under personalisation: A qualitative analysis of work, learning and social inclusion

Statistics suggest that employment is inaccessible to people with intellectual and developmental disabilities. This creates a social, spatial and experiential divide that limits opportunities for social participation and learning. In the UK as elsewhere, social care is framed by ‘personalisation’ policy, which aspires to support personal autonomy yet is associated with a cost-cutting agenda and fragmented provision. The option to employ a Personal Assistant (PA) might support social participation. The conceptual framework for this study is the capability approach, chosen for its focus on the practical opportunities available to people to achieve a life they have reason to value. Building on sociocultural learning theories, the study links work, learning, and social participation or ‘inclusion’. It explores how learning arising through social participation might enhance the capabilities of the people concerned.Video-supported qualitative methods were used. Five young people with intellectual and developmental disabilities took part, each employing a PA and working in a context matching their preferences. For each, a parent, a co-worker or supervisor and the PA took part. Young people were filmed at work. This video supported recall and reflection in semi-structured discussion with participants. Video and discussion content was analysed by case, then thematically, in an iterative process. PA support opened opportunities for social participation outside domestic and disability settings. The contribution of personalisation was ambivalent. People found work through bottom-up initiatives outside ‘social care’ parameters and in implicit challenge to them. Joint negotiation of preferences and opportunities resulted in unpaid work in not-for-profit contexts. Working this way enhanced the capabilities of young people to differing degrees. Collaborative relationships between young people, PAs and people in the workplace underpinned reciprocal learning processes, shown in themes of effort and recognition, mutual adaptation and affiliation. Findings for participatory learning were significant against a backdrop of substantial constraints on young people’s opportunities. This study challenges conceptions of autonomy as solo performance and social norms that delegitimise work outside employment both of which can impede access to participation and reciprocal learning in public settings

Dataset in support of the Southampton doctoral thesis 'The capabilities of people with intellectual and developmental disabilities under personalisation: A qualitative analysis of work learning and social inclusion'

Finding a way to work dataset NVivo files analysed for PhD thesis: The capabilities of people with intellectual and developmental disabilities under personalisation: A qualitative analysis of work learning and social inclusion This dataset if available on request only to bone fide researchers. Please complete the attached request form and return to [email protected]</span

Disability and employment: Finding a way to work.

Disabled people experience low employment rates, low pay and poor quality employment. Disadvantages persist through anti-discrimination and employment support measures. Improving social inclusion is an international goal for disabled people, and high value is placed on employment as the means to attain it. The example of people with intellectual and developmental disabilities in the UK is used in this chapter which draws on the Capability approach and feminist perspectives to argue for participation in ‘work’ – valued shared endeavours – rather than employment at any cost. Relational processes of sociocultural learning and mutual accommodation to extend capabilities and social inclusion are highlighted